Linked Life Data

16445941

Source:http://linkedlifedata.com/resource/pubmed/id/16445941

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2006-3-1
pubmed:abstractText
The topography of the antigen-binding site as well as the number and the positioning of the antigen contact residues are strongly correlated with the size of the antigen with which the antibody interacts. On the basis of these considerations, we have designed a focused scFv repertoire biased for haptens, designated the cavity library. The hapten-specific scFv, FITC8, was used as a scaffold for library construction. FITC8, like other hapten binders, displays a characteristic cavity in its paratope into which the hapten binds. In five of the six complementarity-determining regions, diversity-carrying residues were selected rationally on the basis of a model structure of FITC8 and on known antibody structure-function relationships, resulting in variation of 11 centrally located, cavity-lining residues. L3 was allowed to carry a more complex type of diversity. In addition, length variation was introduced into H2, as longer versions of this loop have been shown to correlate with increased hapten binding. The library was screened, using phage display, against a panel of five different haptens, yielding diverse and highly specific binders to four of the antigens. Parallel selections were performed with a library having diversity spread onto a greater area, including more peripherally located residues. This resulted in the isolation of binders, which, in contrast to the clones selected from the cavity library, were not able to bind to the soluble hapten in the absence of the carrier protein. Thus, we have shown that by focusing diversity to the hotspots of interaction a library with improved hapten-binding ability can be created. The study supports the notion that it is possible to create antibody libraries that are biased for the recognition of antigens of pre-defined size.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0022-2836
pubmed:author
pubmed:issnType
Print
pubmed:day
24
pubmed:volume
357
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
607-20
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
A focused antibody library for improved hapten recognition.
pubmed:affiliation
Department of Immunotechnology, Lund University, P.O. Box 7031, SE-220 07 Lund, Sweden.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't